Chronic transplant dysfunction (CTD) after renal transplantation is characterized by renal function decline and proteinuria.
One-year graft survival after renal transplantation has steadily improved from approximately 40% in the 1970's to more than 90% nowadays (Merville P. Combating chronic renal allograft dysfunction: optimal immunosuppressive regimens. Drugs 2005; 65(5):615-631; http://www.unos.org 2008, Ref Type: Generic). Long-term graft survival, however, has not paralleled this improvement. Approximately half of all cadaveric renal allografts are lost within 10-12 years after transplantation (Hariharan S, Johnson C, Bresnahan B, Taranto S, McIntosh M, Stablein D. Improved Graft Survival after Renal Transplantation in the United States, 1988 to 1996. N Engl J Med 2000; 342(9):605-612). One leading cause is late allograft failure in association with chronic transplant dysfunction (CTD) (Kreis H A, Ponticelli C. Causes of late renal allograft loss, chronic allograft dysfunction, death, and other factors. Transplantation 2001; 71(11 Suppl): SS5-SS9). Currently, there are no good biomarkers to predict the development of CTD (Marsden P A. Predicting outcomes after renal transplantation-new tools and old tools. N Engl J Med 2003; 349(2):182-184).
There is an emerging notion in the renal transplant community that the pathogenesis of CTD includes inflammation (Kreis H A, Ponticelli C. Causes of late renal allograft loss: chronic allograft dysfunction, death, and other factors. Transplantation 2001; 71(11 Suppl):SS5-SS9; Vazquez M A, Jeyarajah D R, Kielar M L, Lu C Y. Long-term outcomes of renal transplantation: a result of the original endowment of the donor kidney and the inflammatory response to both alloantigens and injury. Curr Opin Nephrol Hypertens 2000; 9(6):643-648). Procalcitonin (PCT) has been suggested as a biomarker for bacterial infections and sepsis (Assicot M, Gendrel D, Carsin H, Raymond J, Guilbaud J, Bohuon C. High serum procalcitonin concentrations in patients with sepsis and infection. Lancet 1993; 341(8844):515-518; Becker K L, Nylen E S, White J C, Muller B, Snider R H, Jr. Clinical review 167: Procalcitonin and the calcitonin gene family of peptides in inflammation, infection, and sepsis: a journey from calcitonin back to its precursors. J Clin Endocrinol Metab 2004; 89(4):1512-1525). Recently, it has been found that parenchymal cells stimulated by activated macrophages in infected tissues rather than peripheral blood mononuclear cells underlie very high concentrations of circulating PCT during sepsis (Linscheid P, Seboek D, Schaer D J, Zulewski H, Keller U, Muller B. Expression and secretion of procalcitonin and calcitonin gene-related peptide by adherent monocytes and by macrophage-activated adipocytes. Crit Care Med 2004; 32(8):1715-1721). Animal and human studies have now shown that in sepsis, parenchymal cells (including kidney, liver, lung, muscle and adipocytes) are the principal source of circulating PCT (Linscheid P, Seboek D, Schaer D J, Zulewski H, Keller U, Muller B. Expression and secretion of procalcitonin and calcitonin gene-related peptide by adherent monocytes and by macrophage-activated adipocytes. Crit Care Med 2004; 32(8):1715-1721; Linscheid P, Seboek D, Nylen E S et al. In vitro and in vivo calcitonin I gene expression in parenchymal cells: a novel product of human adipose tissue. Endocrinology 2003; 144(12):5578-5584; Muller B, White J C, Nylen E S, Snider R H, Becker K L, Habener J R Ubiquitous expression of the calcitonin-i gene in multiple tissues in response to sepsis. J Clin Endocrinol Metab 2001; 86(4396-404).
It was surprisingly found that PCT is an independent predictor for late graft failure and/or mortality. Is is, therefore, a promising new biomarker for the prediction of graft loss (GL) and/or mortality.